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Diisopropylethylamine → 3-cyano-N-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-ylmethyl}-propionamide

HRID 68571
ノート
印刷プレビュー

反応式

HRID 68571 の反応式
[C:1]([CH2:3][CH2:4][C:5]([OH:7])=O)#[N:2].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Cl:50][C:51]1[CH:52]=[C:53]([C:58]2([C:71]([F:74])([F:73])[F:72])[O:62][N:61]=[C:60]([C:63]3[S:67][C:66]([CH3:68])=[C:65]([CH2:69][NH2:70])[CH:64]=3)[CH2:59]2)[CH:54]=[C:55]([Cl:57])[CH:56]=1>ClCCl>[C:1]([CH2:3][CH2:4][C:5]([NH:70][CH2:69][C:65]1[CH:64]=[C:63]([C:60]2[CH2:59][C:58]([C:53]3[CH:54]=[C:55]([Cl:57])[CH:56]=[C:51]([Cl:50])[CH:52]=3)([C:71]([F:73])([F:74])[F:72])[O:62][N:61]=2)[S:67][C:66]=1[CH3:68])=[O:7])#[N:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2630863-Cyanopropanoic acidHCID 2724699PyBOPHCID 68293128C-{5-(5-[3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-yl}-methylamine

生成物 1

HCID 867066493-cyano-N-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-ylmethyl}-propionamide
収率 19.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

3-Cyanopropionic acid (104 mg) and PyBOP (400 mg) are added to a solution of DIPEA (0.36 ml) and C-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-yl}-methylamine (286 mg, Example 1, step F) in dichloromethane (5 ml). After 4 hours at RT, the reaction is quenched with water. The aqueous phase is separated and further extracted two times with dichloromethane. The organic phases are combined, dried over MgSO4 and concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield 3-cyano-N-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-ylmethyl}-propionamide (compound 1.39, 67 mg) as a beige resin. MS (HPLC/MS): 491 (MH+). Retention time: 1.90 min.

後処理

  1. customthe reaction is quenched with water
  2. customThe aqueous phase is separated
  3. extractionfurther extracted two times with dichloromethane
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified on a semi-preparative HPLC

出典と根拠

ORDレコード
ord-f4278cb2efd143fc9619f1856ebad428
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08822466B2

反応ノート

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このページの内容参加物実験手順後処理出典と根拠反応ノート